# Bioactive Components in Breast Milk Impact Rotavirus Vaccine Response

> **NIH NIH R21** · BAYLOR COLLEGE OF MEDICINE · 2022 · $191,470

## Abstract

PROJECT SUMMARY
Despite the introduction of live attenuated oral rotavirus vaccines (ORVs) in over 100 countries, rotavirus (RV)
remains the leading cause of acute gastroenteritis in children under the age of 5. This is because ORV efficacy
in most low- and middle-income countries (LMICs) is only about 50% compared to nearly 90% efficacy in high-
income countries. These differences are not specific to one vaccine or one country; all WHO pre-qualified ORVs
show sub-optimal efficacy in LMICs. This is also not an issue of vaccine coverage or cold chain requirements
since poor efficacy was observed even within well controlled clinical trials. ORVs have several advantages
including low costs, ease of administration, ability to generate mucosal immunity and generation of herd immunity
through vaccine shedding. Efforts to improve ORV efficacy will therefore have substantial public health impact.
Our long-term goal is to develop evidence-based interventions to improve ORV response in settings with
high disease burden. Critical steps include understanding what factors distinguish vaccine responders from non-
responders within a population and identifying modifiable factors that will enable the development of targeted
interventions. With this objective, we focus on bioactive components in breastmilk. We hypothesize: (i) Bioactive
components in breast milk are key modulators of ORV response, and (ii) A combination of maternal factors and
infant factors will be more predictive of differences in vaccine response than any individual factor. The rationale
for this hypothesis is our recent work demonstrating a role for interactions between human milk oligosaccharides
(HMOs), the milk microbiome and infant gut microbiome in promoting neonatal RV infections. New data also
indicate that consideration of maternal and infant genetic differences in glycan expression provides a more
comprehensive picture of gastrointestinal infections and vaccine responses than previously recognized. In strong
preliminary data, we show that HMOs and the milk microbiome can directly modulate the in vitro infectivity of
Rotavac, an asymptomatic neonatal rotavirus strain-derived ORV used in India’s national immunization program.
Like other ORVs in LMICs, Rotavac also has sub-optimal efficacy but is remarkably cost effective and can
substantially reduce RV-associated burden if vaccine efficacy is improved. HMOs, commensal bacteria and
microbial products have the potential to be developed as prebiotics and probiotics and thus are attractive
candidates for future development as interventions.
In two specific aims we ask: 1) Is the composition and functional activity of breast milk bioactive components
different between vaccine responders and non-responders? 2) Does the combination of maternal factors and
covarying infant factors better predict ORV response than any factor individually?
Our short-term goal is to gain critical insight into the role of breast milk bioactive components in ORV re...

## Key facts

- **NIH application ID:** 10354154
- **Project number:** 1R21AI166578-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Sasirekha Ramani
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $191,470
- **Award type:** 1
- **Project period:** 2022-02-18 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10354154

## Citation

> US National Institutes of Health, RePORTER application 10354154, Bioactive Components in Breast Milk Impact Rotavirus Vaccine Response (1R21AI166578-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10354154. Licensed CC0.

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